Celecoxib inhibits cellular growth, decreases Ki-67 expression and modifies apoptosis in ovarian cancer cell lines.

Academic Article

Abstract

  • BACKGROUND: There is controversy on the safety of inhibitors of cyclooxygenase administered at high doses; however, these drugs have been reported to be effective in the prevention of a variety of human cancers. To determine if celecoxib influences cellular growth, we evaluated several effects in ovarian carcinoma cell lines. METHODS: CAOV3, OVCAR3 and SKOV3 cell lines were exposed to different concentrations of celecoxib (0-100 microM) for 24-96 h. Cellular growth was assessed using a cell viability assay. Immunohistochemistry was performed to evaluate Ki-67 and cleaved caspase-3. Apoptosis was determined by a TUNEL assay, and Western blot was used to determine COX-2 protein expression. RESULTS: We observed a significant decrease in the cellular growth of all cell lines studied exposed to > or = 70 microM of celecoxib for 72 and 96 h (p < 0.02). All cells demonstrated pancytotoxicity at 100 microM of celecoxib. A significant decrease in Ki-67 expression in all cell lines exposed to > or = 30 microM of celecoxib (p < or = 0.05) for 72 h was observed. We observed significant changes in apoptosis and cleaved caspase-3 expression in SKOV3 cells exposed to 50 microM of celecoxib. Downregulation of COX-2 protein expression caused by celecoxib was observed in SKOV3 cells. CONCLUSIONS: We found that celecoxib inhibits cellular growth and proliferation in a dose-dependent manner in all cell lines studied. SKOV3 cells showed an increase in cleaved caspase-3 expression. Additional studies are in progress to evaluate the effects of celecoxib on other aspects of the control of the cell cycle in cancer cells.
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    Keywords

  • Anti-Inflammatory Agents, Non-Steroidal, Apoptosis, Caspase 3, Celecoxib, Cell Growth Processes, Cell Line, Tumor, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Dose-Response Relationship, Drug, Female, Humans, In Situ Nick-End Labeling, Ki-67 Antigen, Ovarian Neoplasms, Pyrazoles, Sulfonamides
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    Author List

  • Vital-Reyes V; Rodríguez-Burford C; Chhieng DC; Oelschlager DK; Reyes-Fuentes A; Barnes M; Grizzle WE
  • Start Page

  • 689
  • End Page

  • 695
  • Volume

  • 37
  • Issue

  • 6